The FDA has been conducting an ongoing safety review of Zofran because it could increase the risk of developing abnormal changes in the electrical activity of the heart, which could in turn result in a possibly fatal abnormal heart rhythm.
When cardiologists refer to “QT interval,” they are identifying the measure of time between the beginning of the Q wave and the end of the T wave in the heart’s electrical cycle. The QT interval basically stands for the electrical depolarization and repolarization of the heart’s ventricles. If the QT interval is lengthened, it may be a signal for a potentially serious arrhythmia. Arrhythmias are problems with the rate of rhythm of the heart.
The FDA has required GlaxoSmithKline (GSK), the maker of Zofran, to conduct a thorough study to determine the extent to which Zofran may cause prolongation of the QT interval. In 2011, GSK was also required to revise its Zofran labels to include a warning to avoid the use of Zofran in patients who are known to have a long QT syndrome (LQTS). Patients with LQTS can experience sudden, uncontrollable, and dangerous cardiac arrhythmias in response to exercise or stress.
So what does all this have to do with Zofran, pregnant mothers, and birth defects? Some authors, most notably a group of Danish researchers looking into this question, have suggested a link between Zofran’s potential to lengthen the QT interval and teratogenicity (the potential to cause birth defects). In particular, they point to the fact that the embryonic heart of all studied species, including humans, is more susceptible than the adult heart to develop cardiac arrhythmias while it is being formed during pregnancy when exposed to QT prolonging drugs such as Zofran.
As we have pointed out in prior posts, Zofran easily crosses the placental barrier in significant amounts. In one study, Zofran was found in all tested fetal tissue in an average concentration of 41% of that circulating in the mother’s bloodstream. With this in mind, the Danish researchers also point out that in several animal studies, a number of other QT prolongation drugs (as is Zofran) were found to cause birth defects in a dose-dependent fashion. Related studies additionally show that this teratogenicity is the result of the QT prolonging drug causing cardiac arrhythmia in the fetus, and interrupting its blood and oxygen supply.
In these animal studies, the most easily induced birth malformations were ventricular septal defects of the heart. And it is exactly this type of birth defect that some researchers have suggested are the result of pregnant mothers taking Zofran during the first trimester of pregnancy. This is the critical stage at which the human heart is formed.